Dengue with liver involvement is associated with serum soluble thrombomodulin and P-selectin levels.

BACKGROUND

The pathogenesis of liver damage in dengue patients has not been clarified. In this study, we sought to identify the factors that are associated with dengue-induced liver damage and evaluate the associations of cytokines/chemokines, including platelets, neutrophils, activated endothelial cells and other inflammatory factors, with liver damage.

METHODS

We collected and analysed clinical data from 106 hospitalized dengue patients and evaluated the serum levels of platelet (soluble P-selectin [sP-selectin] and soluble CD40 ligand [sCD40L]), neutrophil (neutrophil elastase [NE] and neutrophil myeloperoxidase [MPO]) and endothelial cell (soluble thrombomodulin [sTM]) activation markers, as well as inflammatory mediators, including C-X-C motif chemokine ligand 2 (CXCL2), interleukin (IL)-2, IL-4, IL-6, IL-10, tumour necrosis factor-α and interferon-γ (which are associated with liver damage), in 32 patients.

RESULTS

In total, 106 dengue patients were included in this study. The patients were categorized into dengue with warning signs (DwWS), dengue without warning signs (DwoWS) and severe dengue (SD). Twenty-four patients (22%) had DwWS and 1 patient (1%) had SD. Compared with the DwoWS group, the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase levels in the DwWS/SD group were significantly greater (p<0.001, p<0.001 and p=0.001, respectively). A long time to onset (odds ratio [OR] 1.495 [95% confidence interval {CI} 1.063 to 2.101], p=0.021), thrombocytopenia (OR 4.166 [95% CI 1.11 to 15.629], p=0.034) and concomitant fatty liver (OR 6.326 [95% CI 1.57 to 25.493], p=0.009) were risk factors for dengue-related liver dysfunction. Compared with patients with normal liver enzyme levels, serum sP-selectin levels were significantly lower (p=0.012), sTM levels were higher (p=0.047), serum ALT and AST levels were positively correlated with sTM (r=0.411, p=0.02 and r=0.419, p=0.039; respectively) and AST levels were negatively correlated with sP-selectin levels (r=-0.441, p=0.011) in dengue patients.

CONCLUSIONS

Dengue fever with hepatic involvement is related to serum sTM and sP-selectin levels, thus suggesting that platelet and endothelial cell activation may be involved in the pathogenesis of liver damage and can be used as early predictors of dengue liver damage.